Safety is the prime attention of regulatory bodies as it is the critical factor which can destroy even the humankind. Quality system like GLP has a lot tom play in the field of safety assessments to reach its goal. There are various toxicity studies for assessing the degree of its toxicity. Academic research and peer reviewed journals has their own pitfalls as they could not monitor or inspect the studies which has been conducted. This presentation speak about the Importance of safety assessment, various studies to evaluate the safety and Importance of GLP in safety assessment.

2. Importance of GLP in Safety Assessment
- Alex Thomas
December 09, 2017

3. 3
“All things are poison and nothing is
without poison, only the dose permits
something not to be poisonous”
-Paracelsus
(1493-1541)
therapeutic
effect
toxic
effect
increasing dose

4.  Importance of Safety Assessement
 Various Studies To Evaluate Safety
 Importance of GLP in Safety Assessement
4

5. AGROCHEMICALS AND PETROCHEMICALS
COSMETICS
FOODADDITIVES
PACKAGING MATERIALS FOR DRUGS, FOOD, AND FARM PRODUCTS
MEDICAL DEVICES (SYRINGES, CATHETERS, BLOOD TRANSFUSION SETS, DIALYSIS UNITS,
GLOVES, SUTURES AND SO ON)
DRUGS AND
PHARMACEUTICALS
GENETICALLY MODIFIED CROPS AND
GENETICALLY MODIFIED ORGANISMS
CONTRACEPTIVES
(COPPER T, TUBAL RINGS, CONDOMS AND SO ON)
DYESANDDYEINTERMEDIATES
TOYSANDDEVICESMEANTFOR
CHILDREN
5

6. Thalidomide Sales and Malformations
Phocomelia

8. 10,000 children In Europe

9. 9
The inscription on the statue called "the sick child" reads: In
Remembrance of the Dead and Living of the Contergan
disaster.

10. Regulatory Frameworks
• Food and Drug Administration (FDA), USA
• Medicines and Healthcare Products Regulatory Agency
(MHRA),UK
• Therapeutic Goods Administration (TGA), Australia
• REACH - Registration, Evaluation Authorisation and
Restriction of Chemicals (REACH) program, EU
• Central Drug Standard Control Organization (CDSCO),
India
• The Environmental Protection Agency (EPA), USA
• Central Insecticides Board, India
10

11. Regulatory Guidelines
• OECD Guidelines for testing of chemicals
• ICH Guidelines
• Schedule Y Guidelines
• Central Insecticides Board (CIB) Guidelines
• Environment Protection Agency Guidelines
11

12. Two Basic Functions of Toxicology
12
Assess the likelihood of the occurrence of adverse effects
(qualitative)
Is It Safe?
Hazard Identification
Study the nature and mode of action of adverse effects
(quantitative)
At what concentration is it safe?
Dose Response Assessment

13. Various disciplines of Toxicology..!
• Environmental Toxicology
• Occupational (Industrial) Toxicology
• Regulatory Toxicology
• Food Toxicology
• Clinical Toxicology
• Descriptive Toxicology
• Forensic Toxicology
• Analytical Toxicology
• Mechanistic Toxicology
13

14. Toxicology studies
14
Ecotoxicology
Genetic toxicology
General toxciology
Reproduction toxicology studies

15. Algae Growth Inhibition Test
15
Eco toxicology

16. Daphnia
Acute Immobilization Test
Reproduction Test
16

17. Lemna Growth Inhibition Test
17

18. Acute Fish Toxicity Test
18

19. Terrestrial Eco toxicology
19
Honeybee
Acute Oral and Contact Toxicity Test

20. Earthworm
Acute Toxicity Test
Reproduction Toxicity Test
20

21. Silkworm
Acute and chronic Toxicity tests
21

22. Avian
Acute Oral Toxicity Test
Dietary Toxicity Test
22

23. Ames test
To test whether chemical can cause mutations in DNA of the test organism
23
HISTIDINE --
HISTIDINE++
-Needs HISTIDINE
supplement to grow
Salmonella typhimurium
Reverse
mutation
-Without HISTIDINE supplement bacteria grows
Genetic Toxicology

24. Mouse Lymphoma Assay in L5178Y Tk+/- Cells
To detect gene mutation
24
TK+/-
Cell death
If TFT uptake by cells
No mutation
If no TFT uptake by cells
Cell growth
Mutation
TK+/ -
Cell
TFT
Cell
TK- -
Additiion of Trifluorothimidine (TFT)

25. Chromosomal Aberration Assay in Human Lymphocytes
To identify agents that cause structural chrosome abberration in
mammalian cells
25

26. 26
http://www.crios.be/genotoxicitytests/micronucleus_test.htm (accessed on 22-11-2016)
Nucleus
Micro nuclei
Cell
Cell division arrested at
Inter phase
In vitro Micronucleus Assay in Human Lymphocytes
For evaluating DNA damage by detection of micronuclei in the
cytoplasm of interphase cells

27. Comet Assay
Also called single cell gel electrophorosesis (SCGE) is a sensitive and rapid
technique for quantifying and analysis DNA
27
Roger Salvacion Tan, Modulation of Tinospora rumphii and Zinc Salt on DNA Damage in
Quinoline-Induced Genotoxicity and Hepatotoxicity in Male Albino Mice. Advances in Toxicology,
2014, 1-9

28. • Acute Toxicity
• Dermal Irritation
• Eye Irritation
• Skin Sensitization
• Sub chronic Toxicity 28/90-day
• Chronic Toxicity 6/12-month
• Carcinogenicity Studies
28
General Toxicology

29. 29
1. http:// www.petaindia.com/blog/ban-household-product-tests-closer(accessed on 19.11.2016)
2.http://www.peta.org.au/news/can-save-animals-deadly-product-tests (accessed on 19.11.2016
1
2
4

30. 30
1.https://humantoxicologyproject.org/2015/04/13/advances-in-human-relevant-alternatives-
for-inhalation-toxicity-testing-screening/
2.http://www.politicsresources.net/area/uk/ge10/man/parties/animalprotection.html
Inhalation Chamber (Nose only exposure)

31. Developmental & Reproductive Toxicology
• Fertility and Early Embryonic Development to Implantation
Study (Segment I)
• Pre-and Post-natal Development Study (Segment III)
• Embryo-Fetal Development Study (Segment II)
31

32. 32
Stage 2
•Non-clinical -Safety testing
•Toxicology and safety pharmacology studies, with a potential extension
to pharmacokinetics and bioavailability.
GLP
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009, P-3.

33. First, a few words from the wise…
The basic concepts underlying quality systems
are quite simple:
Say what you do,
do what you say,
prove it and
improve it...
33

34. What is GLP?
34

35. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
35

36. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
36

37. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
37

38. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
38

39. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
Planned

40. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
Planned
Performed

41. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
Planned
Performed
Monitored

42. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
Planned
Performed
Monitored
Recorded

43. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
Planned
Performed
Monitored
Recorded
Archived

44. What is GLP?
A quality system concerned with the organisational
process and the conditions under which non-clinical health
and environmental safety studies are
Planned
Performed
Monitored
Recorded
Archived
and Reported
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009, Page
number 7.

45. HISTORY
 GLP is a formal regulation that was created by the FDA
(United states food and drug administration) in 1978.
 Although GLP originated in the United States , it had a
world wide impact.
 Non-US companies that wanted to do business with the
United states or register their pharmacies in the United
States had to comply with the United States GLP
regulations.
 They eventually started making GLP regulations in their
home countries.
 In 1981 an organization named OECD (organization for
economic co-operation and development ) produced GLP
principles that are international standard.
http://ksuweb.kennesaw.edu/~jhendrix//regs/GLP.ppt (accessed on 22.11.2016)

46. WHY WAS GLP CREATED?
• In the early 70’s FDA became
aware of cases of poor
laboratory practice all over the
United States.
• FDA decided to do an in-depth
investigation on 40 toxicology
labs.
• They discovered a lot
fraudulent activities and a lot
of poor lab practices.
• Examples of some of these
poor lab practices found were
1. Equipment not been calibrated
to standard form , therefore
giving wrong measurements.
2. Incorrect/inaccurate accounts
of the actual lab study
3. Inadequate test systems
http://ksuweb.kennesaw.edu/~jhendrix//regs/GLP.ppt (accessed on 22.11.2016)

47. FAMOUS EXAMPLE
 One of the labs that went under
such an investigation made
headline news.
 The name of the Lab was
Industrial Bio Test. This was a big
lab that ran tests for big
companies such as Procter and
Gamble.
 It was discovered that mice that
they had used to test cosmetics
such as lotion and deodorants
had developed cancer and died.
 Industrial Bio Test lab threw the
dead mice and covered results
deeming the products good for
human consumption.
 Those involved in production,
distribution and sales for the lab
eventually served jail time.
http://ksuweb.kennesaw.edu/~jhendrix//regs/GLP.ppt (accessed on 22.11.2016)

48. Advantages of GLP studies over academic
research
48
Academic research
• Developing and evaluating new hypothesis
• Creating novel methods
• Discovering new findings
• Open to wide interpretation and required additional studies
Inconsistent results (novel techniques, test systems,
test item)

49. Peer review journals
•Relies on summarization of experimental procedures and
results
•To judge –internationally recognised, meet scientific
standards, interest level for dessimination to scientific
community
•No examination of study records, or raw data
49

50. Scientific confidence in GLP studies
• Control of experimental variables
• Power (both statistical and biological)
• Universality of results
• Biological plausibility of results
• Uniformity of substances with similar
attributes and effects
50

51. Key areas
1. Resources: Organisation, personnel, facilities and equipment
51
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009.

52. Key areas
1. Resources: Organisation, personnel, facilities and equipment
2. Characterisation: Test items and test systems
52
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009.

53. Key areas
1. Resources: Organisation, personnel, facilities and equipment
2. Characterisation: Test items and test systems
3. Rules: Protocols, standard operating procedures (SOPs)
53
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009.

54. Key areas
1. Resources: Organisation, personnel, facilities and equipment
2. Characterisation: Test items and test systems
3. Rules: Protocols, standard operating procedures (SOPs)
4. Results: Raw data, final report and archives
54
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009.

55. Key areas
55
1. Resources: Organisation, personnel, facilities and equipment
2. Characterisation: Test items and test systems
3. Rules: Protocols, standard operating procedures (SOPs)
4. Results: Raw data, final report and archives
5. Quality Assurance: Independent monitoring of research
processes
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009.

56. GLP Principles: Purpose
 To ensure Safety
56

57. GLP Principles: Purpose
 To ensure Safety
 To promote the development of quality test data.
57

58. GLP Principles: Purpose
 To ensure Safety
 To promote the development of quality test data.
 To provide basis for mutual acceptance of data (MAD) among
countries.
58

59. GLP Principles: Purpose
 To ensure Safety
 To promote the development of quality test data.
 To provide basis for mutual acceptance of data (MAD) among
countries.
 To avoid duplicative testing, thereby saving time and
resources.
59

60. GLP Principles: Purpose
 To ensure Safety
 To promote the development of quality test data.
 To provide basis for mutual acceptance of data (MAD) among
countries.
 To avoid duplicative testing, thereby saving time and
resources.
 To avoid technical barriers to trade.
60

61. GLP Principles: Purpose
 To improve the protection of human health and environment.
61

62. 62
Test Facility Management
Quality Assurance Unit
Test Item Control Office
Archives
Single point control of the study

63. For a GLP inspector, it should be possible to look at
the documentation and to easily find out the
following:
 Who has done the study?
63
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009

64. For a GLP inspector, it should be possible to look at
the documentation and to easily find out the
following:
 Who has done the study?
 How the experiment was carried out ?
64
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009

65. For a GLP inspector, it should be possible to look at
the documentation and to easily find out the
following:
 Who has done the study?
 How the experiment was carried out ?
 Which procedures have been used?
65
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009

66. 66
For a GLP inspector, it should be possible to look at
the documentation and to easily find out the
following:
 Who has done the study?
 How the experiment was carried out ?
 Which procedures have been used?
 Whether there has been any problem and if so How it has
been addressed and solved where applicable?
Anonymous, Hand book Good laboratory Practice(GLP), 2nd edition, WHO, 2009

67. In FDA-speak:
“If it is not documented . . .
it did not happen!
or, it’s a rumor!”

68. alexthomas.a@gmail.com

69. JAI HIND